Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand.
Ann Neurol. 2016 Aug;80(2):185-201. doi: 10.1002/ana.24694. Epub 2016 Jun 24.
Numerous studies have focused on striatal neurodegeneration in Huntington disease (HD). In comparison, the globus pallidus (GP), a main striatal output nucleus, has received less focus in HD research. This study characterizes the pattern of neurodegeneration in 3 subdivisions of the human GP, and its relation to clinical symptomatology.
Stereology was used to measure regional atrophy, neuronal loss, and soma neuronal atrophy in 3 components of the GP-the external segment (GPe), internal segment (GPi), and ventral pallidum (VP)-in 8 HD cases compared with 7 matched control cases. The findings in the HD patients were compared with HD striatal neuropathological grade, and symptom scores of motor impairment, chorea, cognition, and mood.
Relative to controls, in the HD patients the GPe showed a 54% overall volume decline, 60% neuron loss, and 34% reduced soma volume. Similarly, the VP was reduced in volume by 31%, with 48% neuron loss and 64% reduced soma volume. In contrast, the GPi was less affected, with a 38% reduction in overall volume only. The extent of GP neurodegeneration correlated with increasing striatal neuropathological grade. Decreasing GPe and VP volumes were associated with poorer cognition and increasing motor impairments, but not chorea. In contrast, decreasing GPi volumes were associated with decreasing levels of irritability.
The HD gene mutation produces variable degrees of GP segment degeneration, highlighting the differential vulnerability of striato-GP target projections. The relationship established between clinical symptom scores and pallidal degeneration provides a novel contribution to understanding the clinicopathological associations in HD. Ann Neurol 2016;80:185-201.
大量研究集中在亨廷顿病（HD）的纹状体神经退行性变。相比之下，苍白球（GP）作为主要的纹状体输出核，在 HD 研究中受到的关注较少。本研究描述了人类 GP 的 3 个亚区的神经退行性变模式及其与临床症状的关系。
使用立体学方法测量 8 例 HD 病例与 7 例匹配对照病例中 GP 的 3 个亚区（苍白球外部节段（GPe）、内部节段（GPi）和腹侧苍白球（VP））的区域性萎缩、神经元丢失和神经元体萎缩。将 HD 患者的发现与 HD 纹状体神经病理学分级以及运动障碍、舞蹈病、认知和情绪症状的评分进行比较。
与对照组相比，HD 患者的 GPe 总体体积下降 54%，神经元丢失 60%，神经元体体积缩小 34%。同样，VP 的体积减少 31%，神经元丢失 48%，神经元体体积缩小 64%。相比之下，GPi 的影响较小，仅总体积减少 38%。GP 神经退行性变的程度与纹状体神经病理学分级的增加相关。GPe 和 VP 体积的减少与认知能力下降和运动障碍增加有关，但与舞蹈病无关。相反，GPi 体积的减少与易怒程度的降低有关。
HD 基因突变导致 GP 节段变性程度不同，突出了纹状体-GP 靶投射的不同易损性。临床症状评分与苍白球退化之间的关系为理解 HD 的临床病理关联提供了新的贡献。神经病学杂志 2016；80:185-201。
